Objective: Impulse control disorders (ICDs) in Parkinson disease (PD) are common and can be difficult to manage. The objective of this study was to determine the efficacy and tolerability of naltrexone, an opioid antagonist, for the treatment of ICDs in PD.Methods: Patients with PD (n 5 50) and an ICD were enrolled in an 8-week, randomized (1:1), double-blind, placebo-controlled study of naltrexone 50-100 mg/d (flexible dosing). The primary outcome measure was response based on the Clinical Global Impression-Change score, and the secondary outcome measure was change in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) ICD score.Results: Forty-five patients (90%) completed the study. The Clinical Global Impression-Change response rate difference favoring naltrexone in completers was 19.8% (95% confidence interval [CI] 28.7% to 44.2%). While this difference was not significant (odds ratio 5 1.6, 95% CI 0.5-, p 5 0.5), naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD score over time compared with placebo (regression coefficient for interaction term in linear mixed-effects model 5 27.37, F[df] 5 4.3 [1, 49], p 5 0.04). The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95% CI 9.9-19.9) for naltrexone and 7.5 points (95% CI 2.5-12.6) for placebo.Conclusions: Naltrexone treatment was not efficacious for the treatment of ICDs in PD using a global assessment of response, but findings using a PD-specific ICD rating scale support further evaluation of opioid antagonists for the treatment of ICD symptoms in PD.
Classification of evidence:This study provides Class I evidence that in patients with PD and an ICD, naltrexone does not significantly increase the probability of achieving response. However, the study lacked the precision to exclude an important difference in response rates. Impulse control disorders (ICDs; compulsive gambling, buying, sexual behavior, and eating) occur relatively frequently in Parkinson disease (PD).1 In a large multisite observational study, at least one ICD was identified in 14% of patients with PD.2 ICDs were more common in patients taking a dopamine agonist (DA), which has emerged as the strongest potential risk factor for ICDs. ICD behaviors range widely in severity but can lead to devastating consequences, including financial ruin, divorce, loss of employment, and increased health risks. In general, ICDs are associated with greater functional impairment, 3 decreased quality of life, 4 and increased caregiver burden.
5ICD behaviors can resolve after discontinuing DA treatment, 6 but many patients do not tolerate this intervention, and a DA withdrawal syndrome has been described.7 Deep brain
